AU2004320488A1 - Pharmaceutical composition containing a stable and clear solution of anti-inflammatory drug in soft gelatin capsule and process for producing the same - Google Patents
Pharmaceutical composition containing a stable and clear solution of anti-inflammatory drug in soft gelatin capsule and process for producing the same Download PDFInfo
- Publication number
- AU2004320488A1 AU2004320488A1 AU2004320488A AU2004320488A AU2004320488A1 AU 2004320488 A1 AU2004320488 A1 AU 2004320488A1 AU 2004320488 A AU2004320488 A AU 2004320488A AU 2004320488 A AU2004320488 A AU 2004320488A AU 2004320488 A1 AU2004320488 A1 AU 2004320488A1
- Authority
- AU
- Australia
- Prior art keywords
- weight
- pharmaceutical composition
- soft gelatin
- composition according
- gelatin capsule
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 239000007903 gelatin capsule Substances 0.000 title claims description 48
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 39
- 238000000034 method Methods 0.000 title claims description 21
- 230000008569 process Effects 0.000 title claims description 21
- 239000002260 anti-inflammatory agent Substances 0.000 title claims description 6
- 229940124599 anti-inflammatory drug Drugs 0.000 title claims description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical group CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 96
- 239000000203 mixture Substances 0.000 claims description 45
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 40
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 38
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 claims description 36
- 229960001680 ibuprofen Drugs 0.000 claims description 34
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 34
- 239000002904 solvent Substances 0.000 claims description 27
- 108010010803 Gelatin Proteins 0.000 claims description 25
- 239000008273 gelatin Substances 0.000 claims description 25
- 229920000159 gelatin Polymers 0.000 claims description 25
- 235000019322 gelatine Nutrition 0.000 claims description 25
- 235000011852 gelatine desserts Nutrition 0.000 claims description 25
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 claims description 24
- VTGPMVCGAVZLQI-UHFFFAOYSA-M sodium;2-[4-(2-methylpropyl)phenyl]propanoate;dihydrate Chemical compound O.O.[Na+].CC(C)CC1=CC=C(C(C)C([O-])=O)C=C1 VTGPMVCGAVZLQI-UHFFFAOYSA-M 0.000 claims description 24
- 239000003814 drug Substances 0.000 claims description 22
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 21
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 21
- 235000019441 ethanol Nutrition 0.000 claims description 20
- 235000011187 glycerol Nutrition 0.000 claims description 20
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 18
- 239000008213 purified water Substances 0.000 claims description 18
- XXJWXESWEXIICW-UHFFFAOYSA-N diethylene glycol monoethyl ether Chemical compound CCOCCOCCO XXJWXESWEXIICW-UHFFFAOYSA-N 0.000 claims description 16
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 claims description 13
- 229940079593 drug Drugs 0.000 claims description 13
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid group Chemical group C(CCCCCCC\C=C/CCCCCCCC)(=O)O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 claims description 13
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 claims description 12
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 claims description 12
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 claims description 12
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- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 claims description 12
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 claims description 12
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- WZWGGYFEOBVNLA-UHFFFAOYSA-N sodium;dihydrate Chemical compound O.O.[Na] WZWGGYFEOBVNLA-UHFFFAOYSA-N 0.000 claims description 8
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- 150000003839 salts Chemical class 0.000 description 6
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- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
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- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 4
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- 239000008177 pharmaceutical agent Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- HEFNNWSXXWATRW-JTQLQIEISA-N dexibuprofen Chemical compound CC(C)CC1=CC=C([C@H](C)C(O)=O)C=C1 HEFNNWSXXWATRW-JTQLQIEISA-N 0.000 description 3
- 235000014113 dietary fatty acids Nutrition 0.000 description 3
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- 150000004665 fatty acids Chemical class 0.000 description 3
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- 239000000463 material Substances 0.000 description 3
- 231100000252 nontoxic Toxicity 0.000 description 3
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- PTTPUWGBPLLBKW-UHFFFAOYSA-M sodium;2-[4-(2-methylpropyl)phenyl]propanoate Chemical compound [Na+].CC(C)CC1=CC=C(C(C)C([O-])=O)C=C1 PTTPUWGBPLLBKW-UHFFFAOYSA-M 0.000 description 3
- 235000015112 vegetable and seed oil Nutrition 0.000 description 3
- 239000008158 vegetable oil Substances 0.000 description 3
- 239000003981 vehicle Substances 0.000 description 3
- SVTBMSDMJJWYQN-UHFFFAOYSA-N 2-methylpentane-2,4-diol Chemical compound CC(O)CC(C)(C)O SVTBMSDMJJWYQN-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 229920000858 Cyclodextrin Polymers 0.000 description 2
- 239000001116 FEMA 4028 Substances 0.000 description 2
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 2
- -1 Polyoxyethylene Polymers 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
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- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 description 2
- 231100000716 Acceptable daily intake Toxicity 0.000 description 1
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- 241000700199 Cavia porcellus Species 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
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- 239000004472 Lysine Substances 0.000 description 1
- CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
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- 150000007513 acids Chemical class 0.000 description 1
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- 230000004054 inflammatory process Effects 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
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- 159000000003 magnesium salts Chemical class 0.000 description 1
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- FJQXCDYVZAHXNS-UHFFFAOYSA-N methadone hydrochloride Chemical compound Cl.C=1C=CC=CC=1C(CC(C)N(C)C)(C(=O)CC)C1=CC=CC=C1 FJQXCDYVZAHXNS-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
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- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
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- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
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- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
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- A—HUMAN NECESSITIES
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- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
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- A—HUMAN NECESSITIES
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- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4858—Organic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4866—Organic macromolecular compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
Description
WO 2005/120459 PCT/IN2004/000158 PHARMACEUTICAL COMPOSITION CONTAINING A STABLE AND CLEAR SOLUTION OF ANTI-INFLAMMATORY DRUG IN SOFT GELATIN CAPSULE AND PROCESS FOR PRODUCING THE SAME [0001] Field of the Invention [0002] In general, this invention relates to a pharmaceutical composition containing non-steroidal anti-inflammatory agent. More particularly the present invention provides for a pharmaceutical composition containing substantially stable and clear solution of Ibuprofen Sodium dihydrate encapsulated into soft gelatin capsules and process for producing the same. [0003] Background of the Invention [0004] Ibuprofen is chemically 2-(4-Isobutylphenyl) Propionic acid, practically insoluble in water. It is a very effective Non steroidal anti inflammatory drug (NSAID), analgesic (pain reliever), and antipyretic (fever reducer). NSAID is the general term used for a group of drugs that are effective in reducing inflammation and pain. [0005] The major problem of developing pharmaceutical formulations is to address the poor solubility in water and unpleasant taste of pharmaceutical drugs and the subsequent poor bioavailability. To solve these problems different approaches are taken like developing suspensions, solubilizing in organic solvents, using salts of the drugs, developing prodrugs and using different types of drug delivery systems. [0006] Ibuprofen (racemic mixture) or (S)-(+)-Ibuprofen are not soluble in water, but the sodium dihydrate salt of Ibuprofen is freely soluble in water. It has been found that the usual sodium, calcium and magnesium salts of Ibuprofen also have a discernible disagreeable taste like the acidic drug Ibuprofen.
WO 2005/120459 PCT/IN2004/000158 [0007] The freely water-soluble Ibuprofen Sodium dihydrate makes a good candidate for preparing a pharmaceutical formulation having better bioavailability. The disagreeable taste of the pharmaceutical agent is taken care by using different drug delivery systems. [0008] One such drug delivery system is the soft gelatin, or softgel capsule. The patient compliance is also improved if soft gelatin capsule is used for drug administration, because of its soft, elastic character making it easier to swallow compared to conventional dosage forms like tablets and hard gelatin capsules. [0009] Compared to direct oral liquid administration, the encapsulation of the liquid in soft gelatin capsule has benefits of non-spillage, encapsulation of active agents having non-agreeable taste, provide unit dose of medicament avoiding the need of measuring the liquid medicament. Soft gels dissolve rapidly and release the liquid medicament for ready absorption. [0010] Filled one-piece soft gel capsules have been widely known and used for many years and for a variety of purposes. Because soft gel capsules have properties, which are different from conventional two-piece hard shell capsules, the soft gel capsules are capable of retaining liquid fill material. Another drug delivery issue is content uniformity. If a formulation is a true solution, content uniformity can be achieved. The active ingredient may be completely dissolved in a sofigel formulation. [0011] In general, not all liquids are suitable as vehicles or carriers for inclusion in soft gel capsules. For example, water, propylene glycol, glycerin, low molecular weight alcohols, ketones, acids, amines and esters cannot be used as a carrier in soft gel capsules by themselves since they interact with the gel and, if present, they can only be present in relatively small amounts. [0012] Another limitation associated with soft gel capsules is the inability to incorporate a single dose of the pharmaceutically active ingredient in solution, in an acceptable fill volume. Often, it is difficult to dissolve the pharmaceutically 2 WO 2005/120459 PCT/IN2004/000158 active ingredient in a volume of solvent small enough to incorporate in a soft gel capsule, which delivers the desired dosage amount, is economically appropriate and comfortable to ingest by the patient. Developing solvent systems for pharmaceutically active ingredients that neither significantly interact with the active ingredient nor with the soft gel casing itself, has proven a difficult art. [0013] Related Art [0014] United States Patent No. 6,525,214 to Armitage, et al., discloses the use of S(-)sodium 2-(4-isobutylphenyl)propionate in pharmaceutical compositions and the process to prepare S(-)sodium 2-(4-isobutylphenyl) propionate. Different dosage forms like solid dosage form, oral liquid compositions and compositions for topical administration are disclosed in this Patent. [0015] United States Patent No. 5,510,385 to Stroppolo, et al., discloses a pharmaceutical composition comprising a salt of S(+)-Ibuprofen with a basic amino acid selected between L-arginine and L-lysine. The solid dosage forms disclosed are powders, granulates, tablets and capsules. Use of sweetening agents, flavoring agents, diluents, disintegrating agents, lubricating agents (Polyethylene glycol) and thickening agents (Polyvinylalcohol, Polyvinylpyrrolidone) is disclosed. [0016] United States Patent No. 5,696,165 to Armitage, et al., discloses solid or semi-solid pharmaceutical compositions comprising S(-)sodium 2-(4 isobutyl)propionate having an enantiomeric purity of at least 90% as the sole form of 2-(4-isobutylphenyl)propionate. Also disclosed is the use of S(-)sodium 2-(4-isobutyl)propionate as dihydrate form. The dosage forms disclosed are tablets, capsules, cream, ointment, gel, poultice or patch. [0017] United States Patent No. 6,242,000 to Armitage, et al., discloses a pharmaceutical composition comprising S(-)sodium 2-(4 isobutylphenyl)propionate dihydrate having an enantiomeric purity of at least 3 WO 2005/120459 PCT/IN2004/000158 90%; and a pharmaceutically acceptable carrier. The dosage forms disclosed are tablets, granules, capsules, liquid dosage forms, gel, suppository, etc. [0018] United States Patent No. 5,541,227 to Loew, et al., discloses an Ibuprofen containing medicament which contains Ibuprofen only in the (S)-(+) form in a tablet dosage form which permits reduction of the quantity of active ingredient and the size of the tablet or dragee. This patent discloses solubilised form of either Ibuprofen or Dexibuprofen. [0019] United States Patent No. 4,690,823 to Lohner, et al., discloses the Ibuprofen containing soft gelatin capsules and process for preparing the same. This particular invention makes use of about 70 to 85% by weight of polyoxyethylene-polyoxypropylene polymer or mixture of from 30 to 76% parts by weight of polyalkylene glycol and from 7 to 40% by weight of surfactants to dissolve about 15 to 30% parts by weight of Ibuprofen. [0020] United States Patent No. 6,294,192 to Patel, et al., discloses a triglyceride free composition of hydrophobic therapeutic agents and a carrier, where the composition forms a clear, aqueous dispersion of the surfactants containing the therapeutic agent upon dilution with an aqueous solvent. The carrier of the said composition is made of a hydrophilic surfactant and a hydrophobic surfactant. Ibuprofen is disclosed as one of the therapeutic agents among the hydrophobic therapeutic agents. Ethyl alcohol and Transcutol are disclosed as solubilizers among a group of solubilizers used in the composition. Also disclosed herein is the encapsulation of the composition in a hard or soft gelatin capsule. [0021] United States Patent No. 6,267,985 to Chen, et al., discloses unique pharmaceutical compositions, which form clear aqueous dispersions upon mixing with an aqueous solution. Disclosed herein is the compositions including triglycerides and a combination of surfactants that can solubilize therapeutically effective amounts of therapeutic agents in homogeneous, single-phase systems, which are thermodynamically stable and optically clear. Transcutol is used as one 4 WO 2005/120459 PCT/IN2004/000158 of the solubilizers. Ibuprofen is disclosed as one of the therapeutic agents. The pharmaceutical composition can be preconcentrate in a liquid, semi-solid or solid form or as aqueous or organic diluted preconcentrate. Dosage form disclosed is not limited. [0022] United States Patent No. 5,019,563 to Huntel, et al., discloses complexes of beta-cyclodextrin with various salts of Ibuprofen in which the molar ratios of Ibuprofen to beta-cyclodextrin are within the range of from 1:0.2 to 1:0.75. The preferred salt of Ibuprofen is the sodium salt. The compositions disclosed in this invention are granules or tablets, which further include an amount of a pharmaceutically acceptable acid salt such as sodium citrate or a buffer system such that when the composition is added to water, the pH of the resultant solution is between 6.0 and 8.0. [0023] United States Patent No. 6,221,391 to Rouffer, teaches the self emulsifying Ibuprofen solution in soft gelatin capsule for use therewith. Polyoxyethylene castor oil derivatives have been used in this formulation to provide self emulsifying properties to the formulation. [0024] United States Patent No. 6,251,426 to Gullapalli, discloses Ibuprofen containing softgels wherein Ibuprofen is present as free acid form and softgel capsules are comprised of a gelatin sheath enclosing such fill formulations. Such formulations are prepared by dissolving more than 30% of Ibuprofen in free acid form in polyethylene glycol and at least 10% by weight of polyvinylpyrrolidone having an average molecular weight of from about 2,000 to about 54,000. This formulation may make use of surfactants to increase bioavailability of Ibuprofen. [0025] United States Patent No. 5,071,643 to Yu, et al., discloses the use of a water based solvent system for enhancing the solubility of an acidic, basic or amphoteric pharmaceutical agent, such as Ibuprofen, to produce a highly concentrated solution suitable for encapsulation. The solvent system includes polyethylene glycol containing 0.2 to 1.0 mole equivalents of an ionizing agent per mole equivalent of pharmaceutical agent and 1 to 20% water. This water 5 WO 2005/120459 PCT/IN2004/000158 based solvent system provides for a highly concentrated solution capable of encapsulation into a small enough vessel, such as a softgel capsule, to permit easy swallowing and to provide a pharmaceutically effective dose of a pharmaceutical agent such as Ibuprofen. [0026] United States Patent No. 6,436,430 to Mulye, is directed to a pharmaceutical composition comprising a pharmaceutically effective amount of a lipophilic drug in association with a pharmaceutical carrier, said carrier comprising a lipophilic drug solubilizing effective amount of a propylene glycol monoester of C6 to C18 fatty acid having at least 60% by weight monoester based on the total weight of the propylene glycol ester and a non-ionic surfactant. The lipophilic drugs disclosed in this invention include Ibuprofen, Naproxen and Paclitaxel. [0027] None of the above-cited prior arts disclose specifically, the utilization of Ibuprofen Sodium dihydrate as source of Ibuprofen. [0028] Summary of the Invention [0029] In order to provide better patient compliance, embodiments of the present invention include a pharmaceutical composition comprised in a soft gelatin capsule, the composition containing a clear and stable solution of sodium dihydratate salt of ibuprofen by employing a system of solubilizer and co solubilizer. [0030] In one particular embodiment, the present invention provides for soft gelatin capsules of a pharmaceutical composition comprising about 30.0% to 35.0% by weight of Ibuprofen sodium dihydrate, about 55.0% to 65.0% by weight of Oleic acid as a solubiliser, about 0.6% to 1.2% by weight of Polyvinylpyrrolidone as an agent to improve solubility, about 4.0% to 5.0% by weight of Propylene glycol as a co-solubilizing agent and about 0.3% to 0.7% by weight of Vitamin E as an antioxidant. 6 WO 2005/120459 PCT/IN2004/000158 [0031] In another embodiment, the present invention provides for soft gelatin capsules of a pharmaceutical composition comprising about 20.0% to 22.0% by weight of Ibuprofen sodium dihydrate, about 70.0% to 75.0% by weight of Diethylene glycol monoethyl ether as a solubiliser, about 0.8% to 1.2% by weight of Polyvinylpyrrolidone as an agent to improve solubility and about 3.0% to 5.0% by weight of Propylene glycol as a co-solubilizing agent. [0032] In yet another embodiment, the present invention provides for soft gelatin capsules of a pharmaceutical composition comprising about 28.0% to 30.0% by weight of Ibuprofen sodium dihydrate, about 9.0% to 11.0% by weight of Ethyl alcohol as a solubiliser, about 4.0% to 6.0% by weight of Propylene glycol as an agent to improve solubility and about 50.0% to 60.0% by weight of Polyethylene glycol 400 as a co-solubilizing agent. [0033] In accordance with still another preferred embodiment, there is provided a process for producing soft gelatin capsule containing a substantially stable and clear solution of sodium dihydrate salt of ibuprofen, the process comprising premixing the solubilizer and co-solubilizer, followed by addition of Ibuprofen sodium dihydrate and further mixing, and disposing the resultant into soft gelatin capsules. [0034] In accordance with still another preferred embodiment, there is provided a process for producing soft gelatin capsule containing a substantially stable and clear solution of sodium dihydrate salt of ibuprofen, the process comprising of solubilizing Polyvinylpyrrolidone in Propylene glycol, adding Oleic acid to it, followed by addition of Ibuprofen sodium dihydrate and Vitamin E and further mixing and encapsulating the same into soft gelatin capsules. [0035] In accordance with still another preferred embodiment, there is provided a process for producing soft gelatin capsule containing a substantially stable and clear solution of sodium dihydrate salt of ibuprofen, the process comprising of solubilizing Polyvinylpyrrolidone in Propylene glycol, adding Diethylene glycol monoethyl ether to it, followed by addition of Ibuprofen 7 WO 2005/120459 PCT/IN2004/000158 sodium dihydrate and further mixing, and encapsulating the same into soft gelatin capsules. [0036] In accordance with still another preferred embodiment, there is provided a process for producing soft gelatin capsule containing a substantially stable and clear solution of sodium dihydrate salt of ibuprofen, the process comprising of solubilizing Ibuprofen sodium dihydrate in a mixture of Ethyl alcohol, Propylene glycol and Polyethylene glycol and further mixing, and encapsulating the same into soft gelatin capsules. [0037] In still another preferred embodiment, there is provided shell composition of soft gelatin capsule comprising of about 45.0% by weight of Gelatin, about 20% by weight of Glycerin, and about 35% by weight of Purified water. [0038] In still another preferred embodiment, there is provided shell composition of a soft gelatin capsule comprising of about 45.0% by weight of Gelatin, about 14% by weight of Glycerin, about 9% by weight of Sorbitol solution, and about 32% by weight of Purified water. [0039] In still another preferred embodiment, there is provided shell composition of a soft gelatin capsule comprising of about 50.0% by weight of Gelatin, about 18% by weight of Glycerin, and about 32% by weight of Purified water. [0040] In still another preferred embodiment, there is provided shell composition of a soft gelatin capsule comprising of about 40.0% by weight of Gelatin, about 16% by weight of Glycerin, and about 44% by weight of Purified water. [0041] In still another preferred embodiment, there is provided shell composition of a soft gelatin capsule comprising of about 48.0% by weight of 8 WO 2005/120459 PCT/IN2004/000158 Gelatin, about 20% by weight of Anidrisorb 85/70, and about 32% by weight of Purified water. [0042] In still another preferred embodiment, there is provided shell composition of a soft gelatin capsule comprising of about 45.0% by weight of Gelatin, about 14% by weight of Glycerin, about 9% by weight of Anidrisorb 85/70 and about 32% by weight of Purified water. [0043] Detailed Description of the Invention [0044] The present invention provides, stable and clear solution of Ibuprofen sodium dihydrate in soft gelatin capsules, which when taken orally release the contents of capsule into media of gastrointestinal tract. Since this formulation contains Ibuprofen sodium dihydrate, which is water soluble, does not precipitate in the contents of gastrointestinal tract, present invention does not necessarily calls for addition of any Surfactant/s in formulation, because of inherent property of Ibuprofen sodium dihydrate being water soluble. [0045] To get a stable and clear solution of Sodium dihydrate salt of Ibuprofen we conducted solubility studies on various solubilizing agents and co solubilizing agents, including Polyethylene glycols, propylene glycol, Triacetin, Ethyl alcohol, Polyethylene glycol, esters of fatty acids, Propylene glycol esters of fatty acids, Glycerin, Oleic acid etc. separately and mixture thereof. We discovered that a system containing Oleic acid, Propylene glycol and Polyvinylpyrrolidone with Vitamin E, a system containing Diethylene glycol monoethyl ether, Propyleneglycol and Polyvinylpyrrolidone, and a system containing Ethyl alcohol, Propyleneglycol and Polyethylene glycol has resulted in stable and clear solution of Ibuprofen sodium dihydrate suitable for encapsulation into soft gelatin capsules. [0046] Diethylene glycol monoethyl ether is commercially available as Transcutol HP/Transcutol (Gattefosse). Diethylene glycol monoethyl ether solubilizes drugs that are commonly thought to be insoluble or difficult -to 9 WO 2005/120459 PCT/IN2004/000158 solubilize. It is soluble in water, ethanol, hexylene glycol and propylene glycol and is partially soluble in vegetable oil. LD50 of Transcutol is 7.5 mg/kg (oral route - rat). (Ref: European pharmacopoeia, Transcutol Product Profile, supplied by M/s Gattefosse - France) [0047] Propylene glycol is used in wide variety of pharmaceutical formulations and is generally regarded as a nontoxic material. It is used as solvent, antimicrobial preservative, disinfectant, humectant, plasticizer, water miscible cosolvent and stabilizer for vitamins. Propylene Glycol is a clear, colorless, viscous, practically odorless liquid with a sweet, slightly acrid taste resembling glycerin. It is official in British Pharmacopoeia and USP. Propylene glycol is used in a wide variety of pharmaceutical formulations and is generally regarded as a nontoxic material. Based on metabolic and toxicological data, the WHO has set an acceptable daily intake of propylene glycol at up to 25 mg/kg body weight. (Ref: Handbook of Pharmaceutical Excipients, 2nd edition, P. No: 407-408) [0048] Inclusion of Polyethylene Glycol 400 was found to be useful. Polyethylene Glycols can be used to enhance the aqueous solubility or dissolution characteristics of poorly soluble drugs. Polyethylene glycols are also called as Macrogols. Macrogols are relatively stable, non-toxic compounds, which have a range of properties depending on their molecular weight. They are widely used in pharmaceutical manufacturing as water soluble bases for topical preparations and suppositories, as solvents and vehicles, and as solubilising agents, tablet binders, plasticizers in film coating, and tablet lubricants. They have also been reported to have antibacterial properties. (Ref: Martindale, The Complete Drug Reference 33rd edition, P. No. 1630) [0049] Polyvinylpyrrolidone (PVP K-30) has been used in a variety of Pharmaceutical formulations. It has a property of increasing viscosity and an ability to increase solubility of poorly soluble active drugs. It is used in this formulation to enhance the solubility of Ibuprofen sodium dihydrate and to 10 WO 2005/120459 PCT/IN2004/000158 prevent the recrystallisation. (Ref: Handbook of Pharmaceutical Excipients, 2nd edition, P. No: 392) [0050] Ethyl alcohol is also called as Alcohol or Ethanol. Alcohol is a clear, colorless, mobile and volatile liquid with a slight, characteristic odor and burning taste. Alcohol is a powerful solubiliser for the drugs that are commonly thought to be insoluble or difficult to solubilise. Alcohol is miscible with chloroform, ether, glycerin and water. Ethanol and aqueous solutions are widely used in a variety of pharmaceutical formulations and cosmetics. LD50 (Guinea Pig, Oral) is 5.56 g/kg, LD50 (Mouse, Oral) is 7.5 g/kg, LD50 (Rat, Oral) is 7.06 g/kg and LD50 (Rabbit, Oral) is 6.3 g/kg. (Refer: Handbook of Pharmaceutical Excipients, 2nd edition, P. No: 7 to 8) [0051] Oleic acid is chemically (Z)-9-Octadecenoic acid and is used as a vehicle in manufacturing of soft gelatin capsules. Oleic acid is yellowish to pale brown, oily liquid with a characteristic odor. LD50 (mouse, IV) = 0.23 g/kg, LD50 (rat, IV) = 2.4 mg/kg and LD50 (rat, oral) = 74.0 g/kg. Oleic acid is Generally Recognized As Safe (GRAS) and is official in British Pharmacopoeia and United States Pharmacopoeia/National Formulary. (Refer: Handbook of Pharmaceutical Excipients, 2nd edition, P. No: 325) [0052] Vitamin E also called tocopherols is used as anti-oxidants in the formulation. Inclusion of Vitamin E is advisable in the formulations containing the vegetable oils, such as Oleic acid. Vitamin E is practically insoluble in water; freely soluble in acetone, ethanol, ether and vegetable oil. Vitamin E is Generally Recognized As Safe (GRAS) and is official in British Pharmacopoeia, European Pharmacopoeia and United States Pharmacopoeia. (Ref: Handbook of Pharmaceutical Excipients, 2nd edition, P. No: 12 to 13) [0053] Preferred embodiment is further illustrated in the following examples. These examples illustrate particular embodiments of the invention and are not intended to limit the scope of the invention in any way. 11 WO 2005/120459 PCT/IN2004/000158 Example 1 S. No. Ingredients Quantity (mg) 1 Ibuprofen Sodium Dihydrate 255.00 2. Polyvinylpyrrolidone (PVP K-30) 6.00 3. Propylene glycol 35.00 4. Oleic acid 450.25 5. Vitamin E 3.75 Fill weight/capsule 750.00 Size 11 minim Oblong [0054] Process for preparation: [0055] Solubilising Polyvinylpyrrolidone in Propylene glycol, adding Oleic acid to it followed by addition of Ibuprofen sodium dihydrate and Vitamin E and further mixing; and disposing the solution into soft gelatin capsules. Example 2 S. No. Ingredients Quantity (mg) 1. ibuprofen Sodium Dihydrate 255.00 2. Polyvinylpyrrolidone (PVP K-30) 12.00 3. Propylene glycol 48.00 4. Diethylene glycol monoethyl ether 885.00 Fill weight/capsule 1200.00 . Size 20 minim Oblong [0056] Process for preparation: [0057] Solubilising Polyvinylpyrrolidone in Propylene glycol, adding Diethylene glycol monoethyl ether to it followed by addition of Ibuprofen sodium dihydrate and further mixing; and disposing the solution into soft gelatin capsules. 12 WO 2005/120459 PCT/IN2004/000158 Example 3 S. No. Ingredients Quantity (mg) 1. Ibuprofen Sodium Dihydrate 255.00 2. Ethyl alcohol 85.00 3. Propylene glycol 42.50 4. Polyethylene glycol 467.50 Fill weight/capsule 850.00 Size 14 minim Oblong [0058] Process for preparation: [0059] Solubilising Ibuprofen sodium dihydrate in a mixture of Ethyl alcohol, Propylene glycol and Polyethylene glycol and further mixing; and disposing the solution into soft gelatin capsules. [0060] In general, gelatin shell formulations for soft gelatin capsules comprise of gelatin and one or more plasticizer added to adjust the hardness of the capsule. Typical plasticizers include glycerin, sorbitol and Anidrisorb 85/70. One preferred gelatin formulation for the soft gelatin capsules used in accordance with preferred embodiments includes gelatin in the range of about 40% to 50% by weight and a plasticizer in the range of 15% to 25% by weight. Capsule shell may also include other suitable additives, for example coloring agents, which impart specific characteristics such as the look and feel of the capsule and anti oxidants, opacifiers and etc. FD & C dyes and D & C dyes are examples of pharmaceutically acceptable coloring agents that may be used in the preferred embodiments. [0061] The following examples illustrate the preferred embodiments of soft gelatin shell formulation as used in the present invention. These examples illustrate particular embodiments of the invention and are not intended to limit the scope of the invention in any way. 13 WO 2005/120459 PCT/IN2004/000158 Example 4 Ingredient Percentage by weight Gelatin 45 Glycerin 20 Purified water 35 Example 5 Ingredient Percentage by weight Gelatin 45 Glycerin 14 Sorbitol Solution 9 Purified water 32 Example 6 Ingredient Percentage by weight Gelatin 50 Glycerin 18 Purified water 32 Example 7 Ingredient Percentage by weight Gelatin 40 Glycerin 16 Purified water 44 14 WO 2005/120459 PCT/IN2004/000158 Example 8 Ingredient Percentage by weight Gelatin 48 Anidrisorb 85/70 20 Purified water 32 Example 9 Ingredient Percentage by weight Gelatin 45 Glycerin 14 Anidrisorb 85/70 9 Purified water 32 [0062] Certain modifications and improvements of the disclosed invention will occur to those skilled in the art without departing from the scope of invention, which is limited only by the appended claims. 15
Claims (14)
1. A pharmaceutical composition comprising: a substantially stable and clear solution of an anti-inflammatory drug in a soft gelatin capsule, wherein the solution comprises: Sodium dihydrate salt of Ibuprofen; a solubilizing agent; a co solubilizing agent; Solubility enhancer; and an antioxidant.
2. The pharmaceutical composition according to claim 1, wherein the solubilizing agent is Oleic acid, Diethylene glycol monoethyl ether, Ethyl alcohol.
3. The pharmaceutical composition according to claim 1, wherein co solubilizing agent is Propylene glycol, Polyethylene glycol.
4. The pharmaceutical composition according to claim 1, wherein solubility enhancer is Polyvinylpyrrolidone, Propylene glycol.
5. The pharmaceutical composition according to claim 1, wherein an antioxidant is Vitamin E.
6. A pharmaceutical composition comprising: a substantially stable and clear solution of anti-inflammatory drug in a soft gelatin capsule, wherein the solution comprises: about 30.0% to 35.0% by weight of Ibuprofen sodium dihydrate; about 55.0% to 65.0% by weight of Oleic acid; about 0.6%- to 1.2% by weight of Polyvinylpyrrolidone; about 4.0% to 5.0% by weight of Propylene glycol; and about 0.3% to 0.7% by weight of Vitamin E as an antioxidant. 16 WO 2005/120459 PCT/IN2004/000158
7. A pharmaceutical composition comprising: a substantially stable and clear solution of anti-inflammatory drug in a soft gelatin capsule, wherein the solution comprises: about 20.0% to 22.0% by weight of Ibuprofen sodium dehydrate; about 70.0% to 75.0% by weight of Diethylene glycol monoethyl ether; about 0.8% to 1.2% by weight of Polyvinylpyrrolidone; and about 3.0% to 5.0% by weight of Propylene glycol.
8. A pharmaceutical composition comprising: a substantially stable and clear solution of anti-inflammatory drug in a soft gelatin capsule, wherein the solution comprises: about 28.0% to 30.0% by weight of Ibuprofen sodium dihydrate; about 9.0% to 11.0% by weight of Ethyl alcohol; about 4.0%- to 6.0% by weight of Propylene glycol; and about 50.0% to 60.0% by weight of Polyethylene glycol 400.
9. A process for producing pharmaceutical composition according to any of claims I through to 8, the process comprising: adding Polyvinylpyrrolidone to Propylene glycol with constant mixing; adding Ibuprofen sodium dehydrate to the solution with continuous mixing; adding Vitamin E to the resultant, further mixing to get clear solution; and disposing resulting solution in soft gelatin capsules.
10. A process for producing pharmaceutical composition according to any of claims I through to 8, the process comprising: solubilising Polyvinyl Pyrrolidone in Propylene Glycol with mixing; adding Diethylene Glycol monoethyl ether to the mixture & further mixing; adding Ibuprofen sodium dihydrate to the resultant & further mixing; and disposing resulting solution in soft gelatin capsules. 17 WO 2005/120459 PCT/IN2004/000158
11. A process for producing pharmaceutical composition according to any of claims 1 through to 8, the process comprising: adding Propylene Glycol & Ethyl Alcohol to Polyethylene Glycol 400 & mixing; adding Ibuprofen sodium dihydrate to the mixture & further mixing; and disposing resulting solution in soft gelatin capsules.
12. An orally administrable pharmaceutical composition according to any of claims 1 through to 11 the composition devised into an improved drug delivery device comprising a soft gelatin capsule having a shell comprising about
45.0% by weight of Gelatin, about 20% by weight of Glycerin, and about 35% by weight of Purified water. 13. An orally administrable pharmaceutical composition according to any of claims 1 through to l Ithe composition devised into an improved drug delivery device comprising a soft gelatin capsule having a shell comprising about 45.0% by weight of Gelatin, about 14% by weight of Glycerin, about 9% by weight of Sorbitol solution, and about 32% by weight of Purified water. 14. An orally administrable pharmaceutical composition according to any of claims I through to 11 the composition devised into an improved drug delivery device comprising a soft gelatin capsule having a shell comprising about
50.0% by weight of Gelatin, about 18% by weight of Glycerin, and about 32% by weight of Purified water. 15. An orally administrable pharmaceutical composition according to any of claims I through to 1 Ithe composition devised into an improved drug delivery device comprising a soft gelatin capsule having a shell comprising about 40.0% by weight of Gelatin, about 16% by weight of Glycerin, and about 44% by weight of Purified water. 16. An orally administrable pharmaceutical composition according to any of claims I through to 11 the composition devised into an improved drug 18 WO 2005/120459 PCT/IN2004/000158 delivery device comprising a soft gelatin capsule having a shell comprising about 48.0% by weight of Gelatin, about 20% by weight of Anidrisorb 85/70, and about 32% by weight of Purified water. 17. An orally administrable pharmaceutical composition according to any of claims 1 through to l Ithe composition devised into an improved drug delivery device comprising a soft gelatin capsule having a shell comprising about 45.0% by weight of Gelatin, about 14% by weight of Glycerin, about 9% by weight of Anidrisorb 85/70 and about 32% by weight of Purified water. 18. A pharmaceutical composition as substantially herein described with reference to the description and the examples. 19
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PCT/IN2004/000158 WO2005120459A2 (en) | 2004-06-07 | 2004-06-07 | Pharmaceutical composition containing a stable and clear solution of anti-inflammatory drug in soft gelatin capsule and process for producing the same |
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US (1) | US20060286164A1 (en) |
AU (1) | AU2004320488A1 (en) |
BR (1) | BRPI0418885A (en) |
CA (1) | CA2570649A1 (en) |
DK (1) | DK200700007A (en) |
GB (1) | GB2429916A (en) |
MX (1) | MXPA06014185A (en) |
PL (1) | PL381799A1 (en) |
WO (1) | WO2005120459A2 (en) |
ZA (1) | ZA200610513B (en) |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20080317684A1 (en) * | 2006-09-06 | 2008-12-25 | Isw Group, Inc. | Topical Compositions |
US9914968B2 (en) | 2012-09-26 | 2018-03-13 | Cepheid | Honeycomb tube |
FR2997856B1 (en) * | 2012-11-14 | 2015-04-24 | Pf Medicament | DRUG PASTILLE BASED ON IBUPROFEN SODIUM DIHYDRATE |
US9622970B2 (en) * | 2014-05-08 | 2017-04-18 | Yaguang Liu | Pharmaceutical composition containing lutein and antioxidant for treating and preventing human disease |
EP3053598A1 (en) | 2015-02-06 | 2016-08-10 | Faes Farma, S.A. | Calcifediol soft capsules |
GB2595301A (en) * | 2020-05-21 | 2021-11-24 | Reckitt Benckiser Health Ltd | Novel formulation |
Family Cites Families (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3437599A1 (en) * | 1984-10-13 | 1986-04-17 | Dolorgiet GmbH & Co KG, 5205 St Augustin | SOFT GELATINE CAPSULES CONTAINING IBUPROFEN AND METHOD FOR THE PRODUCTION THEREOF |
US5071643A (en) * | 1986-10-17 | 1991-12-10 | R. P. Scherer Corporation | Solvent system enhancing the solubility of pharmaceuticals for encapsulation |
US5519057A (en) * | 1986-11-14 | 1996-05-21 | Johnson & Johnson--Merck Pharmaceuticals Co. | Ibuprofen-containing medicament |
GB8813682D0 (en) * | 1988-06-09 | 1988-07-13 | Reckitt & Colmann Prod Ltd | Pharmaceutical compositions |
UA34430C2 (en) * | 1991-05-13 | 2001-03-15 | Дзе Бутс Компані Плс | S(-)sodium2-(4-isobutyl-phenyl)propionate dihydrate useful for treatment of inflammation, ache and hyperthermia, a pharmaceutical composition based thereon and a process for preparation of s(-)sodium2-(4-isobutyl- phenyl)propionate |
IT1264855B1 (en) * | 1993-06-21 | 1996-10-17 | Zambon Spa | PHARMACEUTICAL COMPOSITIONS CONTAINING S (+) - 2- (4-ISOBUTYLPHENYL) PROPIONIC ACID SALTS WITH BASIC AMINO ACIDS |
US6221391B1 (en) * | 1998-11-23 | 2001-04-24 | Accucaps Industries Limited | Self-emulsifying ibuprofen solution and soft gelatin capsule for use therewith |
CN1236813C (en) * | 1998-12-11 | 2006-01-18 | 药品处理公司 | Self-emulsifying compositions for drugs poorly soluble in water |
US6267985B1 (en) * | 1999-06-30 | 2001-07-31 | Lipocine Inc. | Clear oil-containing pharmaceutical compositions |
US6294192B1 (en) * | 1999-02-26 | 2001-09-25 | Lipocine, Inc. | Triglyceride-free compositions and methods for improved delivery of hydrophobic therapeutic agents |
US6251426B1 (en) * | 1999-09-02 | 2001-06-26 | Banner Pharmacaps, Inc. | Ibuprofen-containing softgels |
-
2004
- 2004-06-07 BR BRPI0418885-3A patent/BRPI0418885A/en not_active IP Right Cessation
- 2004-06-07 US US10/545,601 patent/US20060286164A1/en not_active Abandoned
- 2004-06-07 GB GB0624498A patent/GB2429916A/en not_active Withdrawn
- 2004-06-07 AU AU2004320488A patent/AU2004320488A1/en not_active Abandoned
- 2004-06-07 WO PCT/IN2004/000158 patent/WO2005120459A2/en active Application Filing
- 2004-06-07 MX MXPA06014185A patent/MXPA06014185A/en not_active Application Discontinuation
- 2004-06-07 CA CA002570649A patent/CA2570649A1/en not_active Abandoned
- 2004-06-07 PL PL381799A patent/PL381799A1/en not_active Application Discontinuation
- 2004-06-07 ZA ZA200610513A patent/ZA200610513B/en unknown
-
2007
- 2007-01-04 DK DK200700007A patent/DK200700007A/en not_active Application Discontinuation
Also Published As
Publication number | Publication date |
---|---|
PL381799A1 (en) | 2007-07-09 |
US20060286164A1 (en) | 2006-12-21 |
MXPA06014185A (en) | 2007-04-16 |
ZA200610513B (en) | 2008-06-25 |
WO2005120459A3 (en) | 2006-03-09 |
GB2429916A (en) | 2007-03-14 |
WO2005120459A2 (en) | 2005-12-22 |
GB0624498D0 (en) | 2007-01-17 |
CA2570649A1 (en) | 2005-12-22 |
BRPI0418885A (en) | 2007-11-27 |
DK200700007A (en) | 2007-01-24 |
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